Molecular Playground/Taxol



One of the CBI Molecules being studied in the  University of Massachusetts Amherst Chemistry-Biology Interface Program at UMass Amherst and on display at the Molecular Playground.

Paclitaxel, also called Taxol (Bristol-Myers Squibb), is a plant derived anti-cancer agent that was first isolated from the bark of Pacific yew tree, Taxus brevifolia, in 1971. It is a complex diterpenoid with a bulky, fused ring system as well as a number of hydrophobic substituents. Approved by the FDA in 1992, it is currently being used in the treatment of ovarian, breast and lung cancers. In addition, therapies are being developed for treatment of Alzheimer's and post-heart surgery patients.

Originally, paclitaxel was produced through the extraction of the drug from the bark of Taxus trees. This process was unsustainable because nearly 40,000 trees were required to meet the demands for the drug each year. A semi-synthetic route was developed and utilized for paclitaxel production which used Taxol precursors which can be extracted from the needles of Taxus trees. This process was more sustainable because the Taxus needles could be harvested depending on their seasonal availability without the destruction of the tree. Currently, paclitaxel is being produced through plant cell culture. This was the first plant cell culture production route approved by the FDA for the production of a pharmaceutical.

Docetaxel (Taxotere, sanofi-aventis) is a semi-synthetic analog of Taxol that was discovered during the search for a more easily produced taxane anti-cancer agent. The hydroxyl group modification on docetaxel leads to an increase in the lipid solubility of the drug. It was first approved by the FDA in 1996 and is currently used in the treatment of breast, stomach and prostate cancer. Currently, Taxotere is produced from paclitaxel precursors which are extracted from Taxus brevifolia, the readily available Wester Yew.

Both Taxol and Taxotere bind to cell microtubules, promoting their assembly into bundles and preventing cell mitosis. This eventually leads to the death of the cells. Although the mechanism of action for both drugs is the same, Taxotere has been found to be twice as potent as Taxol.

 Paclitaxel

Molecular Playground Banner: "Paclitaxel (Taxol),a plant-derived natural product to treat cancer"

 Docetaxel